Investigation of CYP2C19 variation (rs4244285) in different Iranian ethnic groups

Recent studies have reported the clinical importance of CYP2C19 polymorphisms in an individualized approach to clopidogrel treatment. Clopidogrel is an antiplatelet drug that prescribed for ACSs and/or following PCI. Conversion of clopidogrel to its active metabolite requires two sequential oxidative steps involving several CYP enzymes. Only 15% of the prodrug is available for transformation to the active agent; the remaining 85% is hydrolyzed by esterases to inactive forms. On the basis of identified CYP2C19 genotypes, individuals typically are categorized as (EMs; *1/*1), (IMs; e.g., *1/*2), or (PMs; e.g., *2/*2). Multiple variations (polymorphisms) in the CYP2C19 gene have been associated with clopidogrel resistance. The wild-type CYP2C19*1 allele is associated with functional CYP2C19-mediated metabolism. The most common CYP2C19 loss-of-function allele is *2 (681G> A; rs4244285). The aims of this study were to evaluate the frequency of CYP2C19*2 polymorphism and to identify the clopidogrel predicted metabolic phenotypes according to different Iranian ethnic groups. 150 subjects of the general population of 6 ethnic groups (Lor, Kord, Fars, Gilaki and Mazani, 25 subject of every ethnicity) of the country were included. Genotypes for the CYP2C19*2 (rs4244285) polymorphism were detected by Tetra ARMS PCR and it was confirmed with sanger sequencing. Of the 150 subjects (mean age 65 ± 20),83 (55.3 %) were female and 76 (50.6%) male. The genotype frequency for the CYP2C19*2 was differently distributed according to ethnicity in the 25 subjects: Lur: GG (68%); GA (28%); AA (4%), Kurd: GG (80%); GA (20%); AA (0%), Turk: GG (60%); GA (28%); AA (12%), Fars: GG (76%); GA (12%); AA (12%), Mazani: GG (88%); GA (8%); AA (4%), Gilaki: GG (76%); GA (12%); AA (12%), respectively. The heterozygote genotype frequency was higher in lur and turk (28%) and was lower in kurd (0%) compared with other ethnic groups. Results in other study: GG (71.5%); GA (28.5%); AA (0%) in the 28 subjects and GG (47%); GA (17.9%); AA (5.2%) in the 615 subjects.

Keywords:

CYP2C19 gene , rs4244285 , different ethnic groups